Taiwan population study finds association between ADHD and adrenal gland dysfunction

According to the World Health Organization, suicide is the second leading cause of death among individuals aged 15 to 29 years. 

A European study team recently released findings of the first meta-analysis to explore the association between clinically diagnosed ADHD in children and adolescents and subsequent suicidality.  

The criteria for study inclusion were: 

• Most participants had to be under 18 at baseline. 

• Longitudinal design, meaning that participants were followed over time. 

• Having an ADHD sample diagnosed in childhood that was followed up for suicidal behavior. 

• Having a control group without ADHD that was followed up for suicidal behavior. 

• That ADHD was clinically diagnosed based on DSM-5 criteria. 

• The total number of participants and of those with suicidal behavior in both the ADHD group and the control group during follow-up were reported. 

All selected studies scored at least eight out of 11 points after quality assessment. The most frequent defect was that it was unclear whether suicidal behavior had occurred before study initiation. 

Meta-analysis of all nine included studies, encompassing more than 4.4 million participants, reported more than threefold greater odds of overall suicidal behavior among children and adolescents previously diagnosed with ADHD, as opposed to children and adolescents not previously diagnosed with ADHD. Study outcomes varied significantly (high heterogeneity) but showed no publication bias. 

Breaking this down into subcategories of risk: 

• Two studies combining 521 participants reported roughly fourfold greater odds of suicidal ideation among those previously diagnosed with ADHD, with negligible heterogeneity. 

• Six studies encompassing a total of more than 87,000 children and adolescents reported more than threefold greater odds of suicide attempt among those previously diagnosed with ADHD, with high heterogeneity. 

• Two studies combining more than 2.6 million participants reported a near-quadrupling of the odds of suicide death among those previously diagnosed with ADHD, with negligible heterogeneity. 

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The team concluded, “the current systematic review and meta-analysis has confirmed previous findings that there is an elevated risk for suicidal behavior in ADHD patients.” They also note, however, that “this relationship is heterogeneous and complex, with significant differences across ADHD subtypes, age groups, sexes, comorbidities, and social issues, all of which play important roles in the development of suicidal behavior.”

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The Newest Non-stimulant Medication for ADHD

Centanafadine, which is currently under investigation as a treatment for ADHD, will be the first triple reuptake inhibitor for the disorder if it is approved by the FDA. It improves norepinephrine, dopamine and serotonin levels. This new medication is not a stimulant, but due to the dopamine component, it has a stimulant-like effect in patients. In adults, two phase 3 trials and a year-long extension have shown sustained benefits and a tolerable safety profile, laying the groundwork for pediatric research.

Based on this study, improvement was already noticeable after the first week and held steady through week 6. The lower dose (164.4 mg) didn’t separate from placebo, reminding us that getting the dose right will be critical. The effect size was smaller than what is seen for stimulants but 50% of patients had excellent outcomes as indicated by reductions in the ADHD-RS of 50% or more.

Side effect patterns look familiar to anyone who prescribes ADHD medications; loss of appetite, nausea and headaches topped the list. About half of teens on the higher dose reported at least one treatment-emergent adverse event, compared with a quarter of those on placebo. Severe reactions were rare but did include isolated liver enzyme spikes, rash, and a few reports of aggression or somnolence. For everyday practice, that translates to routine growth checks, a look at baseline liver function, and clear guidance to families about reporting rashes or mood changes promptly.

The researchers noted that the study had certain limitations, including limited generalizability to adolescents beyond North America, the exclusion of teacher ratings on the ADHD-RS-5 scale and the study’s short duration. They added that future studies should explore long-term treatment outcomes and efficacy compared with other ADHD treatments, as well as its effect on treating ADHD with comorbid conditions.

Why should this matter to clinicians already juggling multiple non-stimulant options for ADHD?

First, speed. Centanafadine separated from placebo within a week. In this regard, it might be closer to stimulants than to the multi-week ramp-up we expect from current non-stimulants. Second, it offers another option when stimulants are contraindicated or poorly tolerated, or when they raise diversion concerns. Its mechanism also makes it intriguing for patients who need both norepinephrine and dopamine coverage but prefer to avoid schedule II drugs. Because it also improves serotonergic transmission, it may be useful for some of ADHD’s comorbidities (see our new article for evidence about serotonin’s role in these disorders).

Keep in mind that centanafadine for ADHD is still investigational, so participation in clinical trials remains the only access route.

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A recent in-depth clinical review published by the American Academy of Neurology examines how ADHD manifests in adulthood and how neurologists can differentiate it from other causes of attention problems. 

Recognition of ADHD in adults by clinicians is often delayed or misdiagnosed due to overlapping symptoms with anxiety, depression, sleep disorders, and life stressors. Conversely, as ADHD in adults becomes more widely acknowledged, largely due to increased public awareness and social media trends, clinicians need to take extra care not to incorrectly diagnose patients with ADHD. This publication aims to shine a light on both sides of this issue and highlight the importance of clinicians being trained in proper ADHD screening. 

ADHD Symptom Overlaps and Differential Diagnosis 

The article highlights how many adults come to neurology clinics convinced they have ADHD after online quizzes or watching others get diagnosed. True ADHD must be differentiated from issues with shared signs and symptoms such as poor sleep, anxiety, depression, or even OCD or Bipolar Disorder. This is a high-level clinical skill called differential diagnosis.

• Sleep Issues- This is one of the most common causes of attention and focus problems that resemble ADHD in adults. Chronic sleep deprivation can lead to issues like distractibility, forgetfulness, and emotional instability, which may be mistaken for ADHD symptoms, especially if people don’t realize how long-term sleep loss has affected them. Clinicians are encouraged to ask about sleep habits and use tools like the Epworth Sleepiness Scale.

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• Anxiety Disorders- Anxiety is common in adults with ADHD, but a patient with anxiety who does not have ADHD may present with signs and symptoms that overlap with ADHD. A key difference between anxiety and ADHD is that people with ADHD often get distracted even when relaxed or doing something enjoyable without realizing it. Those with anxiety usually feel tense, guilty, and very aware of their distraction.

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• Depression- Depression can cause trouble with focus, energy, and motivation, again, often overlapping with or mimicking symptoms of ADHD. Since both conditions are common, they can also occur together, making it important to look at when symptoms started. If attention problems were present before any depressive episodes, it may point to ADHD, but in unclear cases, treating depression first and then reassessing can help clarify the diagnosis.

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• OCD- Some people with ADHD experience distressing, repetitive thoughts that feel like OCD, even if they haven’t been diagnosed with it. These thoughts can cause anxiety or sadness, even when the person knows they’re unlikely or irrational, but unlike OCD, there are no compulsive behaviors. In some cases, ADHD medication helps reduce these thoughts by improving focus and emotional regulation.

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• Autism- Adults with ASD are more likely to also have ADHD, and in some cases, ADHD symptoms, such as missing social cues or acting impulsively, can be mistaken for autism. This overlap can sometimes make diagnosis more complicated.

The author of the article, Dr. Mierau, provides detailed clinical strategies such as asking open-ended questions, exploring how symptoms show up at home and at work, and watching for patterns like chronic lateness or emotional overeating. (This paper points out that, while not included in the DSM-VI, food cravings and binge behaviors are commonly found in patients with ADHD.)

This review correctly emphasizes that neuropsychological testing is not necessary for diagnosis. Instead, a thorough clinical interview, including a detailed family history and behavioral observation, can be more telling. 

Conclusion: Real Barriers to Proper ADHD Diagnosis

The review article closes with a call to action: the biggest obstacle isn’t diagnosing or treating ADHD, it’s access. Adults struggle with pharmacy shortages, no-refill laws, and insurance hurdles, despite research showing treatment reduces mortality and improves life quality. Dr. Mierau argues for more trained providers, better public education, and policy changes to reduce stigma and expand access.

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